Christopher Beynon

Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

OBJECTIVESnDespite several advantages of the novel anticoagulant rivaroxaban compared with vitamin K antagonists (VKA), its lack of specific antidotes to reverse anticoagulant effects may increase the risk profile of patients with bleeding complications. The purpose of this study was to analyze the effects of pre-injury treatment with rivaroxaban on patients with mild traumatic brain injury (TBI) and traumatic intracranial haemorrhage (tICH).nnnMETHODSnA total of 70 patients with tICH after mild TBI were included in this retrospective analysis and were categorized into three groups: group A (no antithrombotics n=37), group B (antiplatelet medication n=22, VKA=5), and group C (rivaroxaban n=6). Medical charts were reviewed for baseline characteristics, laboratory values, intracranial haemorrhage, repeated computed tomography (CT) scans, re-haemorrhage, Glasgow Coma Scale (GCS) scores and in-hospital mortality.nnnRESULTSnNo significant differences were observed for baseline characteristics. The rate of re-haemorrhage was significantly higher in group C (50%) than in group A (11%) (p<0.05). Two patients died and both had been treated with rivaroxaban which resulted in a significantly higher mortality rate of 33% in group C compared with groups A (0%) and B (0%). No significant differences were observed for GCS at discharge and length of hospital stay between survivors of groups A-C.nnnCONCLUSIONSnDespite major limitations of retrospective design and small patient numbers, our results suggest that rivaroxaban may exacerbate intracranial haemorrhage in patients with mild TBI. Further studies are needed to characterize the risk profile of this drug in patients with tICH.

Multiple electrode aggregometry in antiplatelet-related intracerebral haemorrhage

As the population ages, antiplatelet agents are increasingly used in patients with cardiovascular diseases. Due to impaired platelet activity, these patients are at increased risk for bleeding complications and this is of particular importance in patients with intracerebral haemorrhage. The multiple electrode aggregometry analyser Multiplate (Roche Diagnostics, Mannheim, Germany) was introduced in 2006 to monitor the effectiveness of antiplatelet drugs in interventional cardiology. As a point-of-care device, it allows bedside assessment of platelet activity within minutes through analysis of a sample of whole blood. In patients treated with antiplatelet medication and in need of urgent cardiac surgery, these devices allow prediction of intraoperative blood loss and their use was implemented within respective guidelines to direct transfusion strategies. We used the Multiplate analyser for rapid assessment of antiplatelet activity in a patient who developed an intracerebral haemorrhage after administration of aspirin and clopidogrel. Antiplatelet activity was assessed within 10 minutes while the patient was transferred to the operating room and after transfusion of platelet concentrates and administration of desmopressin and tranexamic acid, repeated Multiplate analysis demonstrated nearly normalized platelet activity. In our view, there is great potential for this device to improve treatment in neurosurgery and especially the treatment of antiplatelet-related intracerebral haemorrhage. Instant assessment of antiplatelet activity or effectiveness of haemostatic measures is facilitated and furthermore, patients with normal platelet activity despite a positive history of antiplatelet medication intake can be identified. In these patients, empiric administration of haemostatic substances would unnecessarily increase the risk of thromboembolic events.

Intracranial Pressure Telemetry: First Experience of an Experimental In Vivo Study Using a New Device

OBJECTIVEnTo test two new telemetric intracranial pressure (ICP) probes (NEUROVENT(®)-P-tel, NEUROVENT(®)-S-tel) in a porcine model. We aimed to intraoperatively correlate the telemetric probes to parenchymal ICP probes and study their reliability in the first hours after implantation. The experimental set-up, new telemetric technology and first data will be presented.nnnMETHODSnWe implanted a right parietal (parenchymal) and left parietal (subdural) telemetric ICP probe in 13 Göttingen mini-pigs under general anaesthesia. Through the left parietal burr hole a parenchymal ICP probe (Neurovent(®) ICP) was introduced. Intraoperatively, the head position was changed to provoke ICP changes every 10 min. The telemetric probes were left in situ and finally the parenchymal ICP probe was removed. We correlated mean differences between each telemetric probe and the conventional ICP measurement and Bland-Altman plots were generated for statistical analysis.nnnRESULTSnWe present first data containing intraoperative measurements of 26 telemetric probes after implantation. Intraoperatively, mean differences of 2.48 ± 1.52 mmHg SD (NEUROVENT(®)-P-tel) and 2.64 ± 1.79 mmHg (NEUROVENT(®)-S-tel) were observed. The Bland-Altman plot demonstrates good correlation of the telemetric probes compared with parenchymal ICP probes.nnnCONCLUSIONnWe present a new telemetric technology that was experimentally compared with a parenchymal ICP probe. We provide data that the new telemetric probes will comparably measure ICP vs an external ICP probe. This stand-alone ICP tool may allow permanent measurement of ICP in hydrocephalus patients. Further continuation of our study will demonstrate whether this system guarantees acceptable long-term reliability.

Rapid bedside coagulometry prior to urgent neurosurgical procedures in anticoagulated patients

Abstract Introduction. With the increased use of oral anticoagulation with vitamin K antagonists, emergency physicians encounter a growing number of patients requiring a rapid reversal of anticoagulant effects in order to perform urgent surgical procedures. Initiation of these procedures can be delayed because the coagulation status has to be assessed through examination of blood samples in central laboratories (CL). This delay may lead to negative effects, especially in potentially life-threatening conditions such as intracranial haemorrhage. Point-of-care (POC) devices for assessment of international normalized ratio (POC INR) have improved the management of anticoagulation therapy in the outpatient setting. The use of these devices may also have beneficial effects in the treatment of anticoagulated patients requiring urgent neurosurgical procedures. The primary aim of this study was to analyse the potential of POC-guided assessment of INR to reduce time to potentially life-saving neurosurgery in this setting. Feasibility and accuracy as well as the gain of time through the use of this device were analysed. Materials and methods. The POC coagulometer CoaguChek XS® was used in 17 patients with a history of anticoagulant use and a condition requiring urgent anticoagulant reversal prior to neurosurgical procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2). Results. No technical difficulties occurred and rapid assessment of INR was achieved in all cases within 2 min. POC INR values correlated well with CL INR assessment with a mean INR deviation of 0.036 ± 0.12. The mean gain of time through the use of the POC INR device compared with CL assessment of INR was 47 ± 6 min (range: 37–61 min). Conclusion. Our initial experiences with a POC INR device in anticoagulated patients undergoing urgent neurosurgical procedures demonstrate that its use may contribute to an improved management of these patients.

Initial experiences with Multiplate® for rapid assessment of antiplatelet agent activity in neurosurgical emergencies

OBJECTIVEnAs the population ages, physicians encounter a growing number of patients who are treated with antiplatelet agents and present with severe conditions requiring urgent neurosurgical therapy. Standard laboratory investigations are insufficient to evaluate platelet activity and furthermore, it is difficult to evaluate effects of haemostatic measures on platelet function. In this article we report our initial experiences with the point-of-care device Multiplate® for assessment of platelet activity in neurosurgical emergencies on patients with a reported intake of antiplatelet medication.nnnMETHODSnMultiplate® assessment of antiplatelet activity was carried out in 21 non-consecutive patients with a reported intake of antiplatelet medication (aspirin: n=21, clopidogrel: n=3, ticragrelor: n=1) and urgent admission to our hospital because of conditions such as intracranial haemorrhage requiring urgent neurosurgical therapy. Analysis was repeated in order to evaluate the effectiveness of haemostatic drugs and platelet concentrate transfusion on platelet activity in six patients.nnnRESULTSnNo technical difficulties occurred and in all cases, results were obtained within 15 min. On admission, patients arachidonic acid induced platelet activity was reduced by 44.4±33.5% (range: -79.7% to +44.3%) compared to the lower reference limit. Two patients had a normal platelet activity despite a reported intake of aspirin. Haemostatic measures significantly increased arachidonic acid induced platelet activity by 100±66% (p<0.005).nnnCONCLUSIONnThe Multiplate® device allowed rapid assessment of antiplatelet agent activity and evaluation of haemostatic measures on platelet activity. Further studies with larger patient numbers are needed, but this device may represent a valuable tool to improve treatment modalities in patients treated with antiplatelet medication and conditions requiring urgent neurosurgical therapy.

Influence of Isoflurane on Neuronal Death and Outcome in a Rat Model of Traumatic Brain Injury

In the developing brain agents clinically used for the purpose of analgosedation can cause severe neurodegeneration. In patients with TBI analgosedation is a first-line treatment for intracranial hypertension. At the same time, damaged neuronal networks undergo conformational changes and use developmental mechanisms to restore brain function. Inhibition of repair mechanisms by sedatives may cause brain dysfunction and neuronal cell death during development and after traumatic brain injury. To test this hypothesis, the influence of sedation was experimentally evaluated in a controlled cortical impact injury model (CCII). One experimental group was preconditioned with regular sedation (isoflurane 1.0 MAC(50)) and the second group with deep sedation (isoflurane 1.67 MAC(50)). After controlled cortical impact injury (CCII) we tested the outcome at 4 h and 48 h using histological methods and a neurological test. Increased apoptosis was found in referenced cortical areas as early as 48 h after trauma (TUNEL-positive cells/field of view, mean ± SEM, 116.6 ± 9.3 and 45.3 ± 4.1, both n = 12). Along with histological findings neurological outcome was worst as indicated by a higher score in the experimental group with deep sedation (mean ± SEM 4 h, 13.9 ± 0.6, n = 14 and 20 ± 0.7, n = 15; 48 h, 8.1 ± 0.6, n = 14 and 13.3 ± 0.6, n = 15). Although blood pressure was lower with deep sedation, no frank hypotension occurred. In our experiments deep sedation with high doses of isoflurane caused neurodegeneration and worse outcome compared with regular sedation.

ANTICOAGULATION REVERSAL WITH PROTHROMBIN COMPLEX CONCENTRATE IN ANEURYSMAL SUBARACHNOID HEMORRHAGE

BACKGROUNDnIntracerebral hemorrhage is a well-recognized complication of anticoagulation therapy. However, there are only a few reports that address the management of aneurysmal subarachnoid hemorrhage (aSAH) in anticoagulated patients.nnnOBJECTIVEnWe report on our experiences with the use of prothrombin complex concentrate (PCC) for rapid anticoagulation reversal in aSAH.nnnMETHODSnWe retrospectively analyzed our institutional database of consecutive patients who received PCC between February 2006 and August 2014 (n > 1000). Data from all anticoagulated patients referred to our hospital for aSAH and those who received PCC were included in this analysis. Patient characteristics as well as treatment modalities were analyzed, with specific focus on results of laboratory examination, PCC administration and bleeding, and thromboembolic complications during the later course.nnnRESULTSnIn total, only 9 patients (< 1% of all aSAH patients treated at our institution during the study period) had been anticoagulated at admission. Median international normalized ratio (INR) of patients at admission was 2.31 (interquartile range [IQR] 1.83-2.97) and after median administration of 2500 IU (IQR 2000-3000 IU) PCC, median INR significantly decreased to 1.15 (IQR 1.07-1.19). Surgical and interventional procedures were initiated within a median of 3.9 h (IQR 1.7-9.3 h) after admission. No hemorrhagic or thromboembolic events occurred later in the course. A favorable outcome according to the Glasgow Outcome Scale (scores of 4 and 5) was achieved in 6 patients (67%).nnnCONCLUSIONSnAneurysmal SAH in anticoagulated patients is a rare condition. PCC is an effective option to rapidly reverse anticoagulation in aSAH and might facilitate achieving a favorable outcome in these patients.

Treatment With Prothrombin Complex Concentrate to Enable Emergency Lumbar Puncture in Patients Receiving Vitamin K Antagonists.

STUDY OBJECTIVEnLumbar punctures are frequently necessary in neurologic emergencies, but effective oral anticoagulation with vitamin K antagonists represents a contraindication. We report the effectiveness of prothrombin complex concentrates to reverse vitamin K antagonist to enable emergency lumbar punctures, as well as evaluate lumbar puncture- and prothrombin complex concentrates-related complications.nnnMETHODSnConsecutive patients treated with prothrombin complex concentrates between December 2004 and June 2014 to enable emergency lumbar puncture were included. International normalized ratio (INR) before and after prothrombin complex concentrates treatment and the time between start of reversal treatment and lumbar puncture were recorded. A target INR of less than or equal to 1.5 was defined as effective prothrombin complex concentrates treatment. Bleeding events, thromboembolic events, and allergic reactions after prothrombin complex concentrates treatment were identified and classified as related, probably, possibly, unlikely related, or not related to the lumbar puncture and prothrombin complex concentrates infusion.nnnRESULTSnThirty-seven patients were included (64.9% men; median age 76.0 years; interquartile range [IQR] 71.0 to 84.0 years). The intervention with prothrombin complex concentrates was effective in 33 of 37 patients (89.2%; 95% confidence interval [CI], 78.4% to 97.3%). The median INR was 2.2 (IQR 1.8 to 2.9; 95% CI, 1.9 to 2.5) before and 1.3 (IQR 1.2 to 1.4; 95% CI, 1.2 to 1.3) after prothrombin complex concentrates treatment. The median time between start of prothrombin complex concentrates treatment and lumbar puncture was 135 minutes (IQR 76 to 266 minutes; 95% CI, 84 to 198 minutes). One clinically irrelevant intracranial subdural hematoma related to the lumbar puncture developed. No allergic reaction was observed, but 2 of 37 patients (5.4%; 95% CI, 0% to 13.5%) experienced a thromboembolic event (1 ischemic stroke, classified unlikely related, and 1 myocardial infarction, possibly related to prothrombin complex concentrates treatment).nnnCONCLUSIONnReversing the effect of vitamin K antagonist with prothrombin complex concentrates to enable emergency lumbar puncture appears effective and safe, particularly in regard to bleeding events.

Emergency neurosurgical care in patients treated with apixaban: report of 2 cases ☆

A debate has emerged regarding the safety profile of direct anticoagulants, which are increasingly prescribed for the prevention of thromboembolic events. Despite favorable safety data derived from controlled clinical trials, the absence of specific antidotes for the management of hemorrhagic complications represents a major challenge for emergency physicians. Here, we present the first report on patients treated with the direct factor Xa inhibitor apixaban and conditions requiring urgent neurosurgical intervention (intracerebral hemorrhage, n = 1; subdural hematoma, n = 1). Prothrombin complex concentrates were administered before surgery, and both patients had a favorable postsurgical course without bleeding or thromboembolic complications. Further studies are needed, but this approach seems to be suitable for the emergency management of apixaban-associated intracranial hemorrhage.

Point-of-Care Testing in Neurosurgery

&NA; Coagulation disorders can have a major impact on the outcome of neurosurgical patients. The central nervous system is located within the closed space of the skull, and therefore, intracranial hemorrhage can lead to intracranial hypertension. Acute brain injury has been associated with alterations of various hemostatic parameters. Point‐of‐care (POC) techniques such as rotational thromboelastometry are able to identify markers of coagulopathy which are not reflected by standard assessment of hemostasis (e.g., hyperfibrinolysis). In patients with acute brain injury, POC test results have been associated with important outcome parameters such as mortality and need for neurosurgical intervention. POC devices have also been used to rapidly identify and quantify the effects of antithrombotic medication. In cases of life‐threatening intracranial hemorrhage, this information can be valuable when deciding over administration of prohemostatic substances or immediate neurosurgical intervention. In elective neurosurgical procedures, POC devices can provide important information when unexpected bleeding occurs or in cases of prolonged operative time with subsequent blood loss. Initial experiences with POC devices in neurosurgical care have shown promising results but further studies are needed to characterize their full potential and limitations.